Musculoskeletal Tissue Research Articles

Maintaining soldier musculoskeletal health using personalised digital humans, wearables and/or computer vision.

The physical demands of military service place soldiers at risk of musculoskeletal injuries and are major concerns for military capability. This paper outlines the development new training technologies to prevent and manage these injuries. Narrative review. Technologies suitable for integration into next-generation training devices were examined. We considered the capability of technologies to target tissue level mechanics, provide appropriate real-time feedback, and their useability in-the-field. Musculoskeletal tissues' health depends on their functional mechanical environment experienced in military activities, training and rehabilitation. These environments result from the interactions between tissue motion, loading, biology, and morphology. Maintaining health of and/or repairing joint tissues requires targeting the "ideal" in vivo tissue mechanics (i.e., loading and strain), which may be enabled by real-time biofeedback. Recent research has shown that these biofeedback technologies are possible by integrating a patient's personalised digital twin and wireless wearable devices. Personalised digital twins are personalised neuromusculoskeletal rigid body and finite element models that work in real-time by code optimisation and artificial intelligence. Model personalisation is crucial in obtaining physically and physiologically valid predictions. Recent work has shown that laboratory-quality biomechanical measurements and modelling can be performed outside the laboratory with a small number of wearable sensors or computer vision methods. The next stage is to combine these technologies into well-designed easy to use products.

EPH47 Active Surveillance for Safety Monitoring of COVID-19 Vaccines in Saudi Arabia

It is generally accepted that the world will not return to the pre-pandemic normally situation until safe and effective vaccines become available. However, the rare and unknown adverse events following immunization (AEFIs) are not usually detected in the clinical trials. Thus, monitoring the safety of coronavirus disease of 2019 (COVID-19) vaccines in real-world population is essential. Therefore, the Saudi Food and Drug Authority (SFDA) performed a post-marketing safety surveillance of AEFIs following administration of COVID-19 vaccines. A prospective cohort study conducted and followed subjects who received COVID-19 vaccines from the first day of vaccination for seven days after the first and second doses, then biweekly for three months. All information from the vaccinee (demographic information, vaccine type and AEFIs) were collected by phone through a standardized online questionnaire. Baseline characteristics and AEFIs were analyzed descriptively by SPSS software. AEFIs classified according to medical Dictionary for Regulatory Activities (MedDRA). 544 subjects of 8867 agreed to be part of the study. Among them, 218 subjects completed the study. Out of 218, 87 (39.91%) individual received Pfizer-BioNTech vaccine, 45(20.64%) received Oxford/AstraZeneca vaccine, 5(2.3%) individual received Moderna vaccine, and 81 (37.2%) received two different COVID-19 vaccines. The reported events were categorized to system organ class (SOC) according to MedDRA. The most reported SOCs were skin and subcutaneous tissue disorders (n=66 with Pfizer-BioNTech vaccine, n=34 with Oxford/AstraZeneca vaccine, n=5 with Moderna vaccine), nervous system disorder(n=20with Pfizer-BioNTech vaccine, n=18with Oxford/AstraZeneca vaccine, n=3with Moderna vaccine) infections and infestations (n=23 with Pfizer-BioNTech vaccine, n=33 with Oxford/AstraZeneca vaccine, n=4 with Moderna vaccine), musculoskeletal and connective tissue disorders (n=53with Pfizer-BioNTech vaccine, n=46 with Oxford/AstraZeneca vaccine, n=7 with Moderna vaccine). Only 10 (4.6%) cases were serious and required medical intervention. The preliminary results shows the short-term safety profiles of included COVID-19 vaccines are acceptable in Saudi Arabia.

Orthopaedic applications of cold physical plasma.

Cold physical plasma (CPP) technology is of high promise for various medical applications. The interplay of specific components of physical plasma with living cells, tissues and organs on a structural and functional level is of paramount interest with the aim to induce therapeutic effects in a controlled and replicable fashion. In contrast to other medical disciplines such as dermatology and oromaxillofacial surgery, research reports on CPP application in orthopaedics are scarce. The present implementation of CPP in orthopaedics involves surface modifications of orthopaedic materials and biomaterials to optimize osseointegration. In addition, the influence of CPP on musculoskeletal cells and tissues is a focus of research, including possible adverse reactions and side effects. Its bactericidal aspects make CPP an attractive supplement to current treatment regimens in case of microbial inflammations such as periprosthetic joint infections. Attributed anticancerogenic and pro-apoptotic effects underline the clinical relevance of CPP as an additive in treating malignant bone lesions. The present review outlines ongoing research in orthopaedics involving CPP; it distinguishes considerations for safe application and the need for more evidence-based research to facilitate robust clinical implementation.

A Model of Mechanotransduction in Polyvinyl Alcohol‐Based Composite Hydrogels for Regulating Musculoskeletal Differentiation

AbstractIn regenerative medicine, extracellular matrix (ECM)‐inspired materials are currently being explored to imitate mechanotransduction pathways and control cell fate. In musculoskeletal tissue regeneration, enhancing mechano‐biological signals require biomaterials that are both biocompatible and viscoelastic and can retain water content. Herein, based on these requirements, various polyvinyl alcohol (PVA)‐based composite hydrogels, reinforced by polyhydroxy butyrate (PHB) nanofibers, are proposed to differentiate equine adipose‐derived stem cells for musculoskeletal regeneration. To study the role of fiber embedding in improving scaffold properties, different nanofiber assemblies, including chopped short ones with random orientation (PVAS), single‐layer (PVAL1), and double‐layer membranes (PVAL2) are positioned into the PVA matrix. PHB reinforcements negatively affect swelling and positively enhanced phase transition temperatures and crystallinity of PVA hydrogel. According to mechanical analysis results, compositing with PHB nanofibrous layers strengthen the PVA matrix due to some restrictions on PVA chain mobility. Gene expression investigations also reveal that higher matrix stiffness after layering with two PHB membranes (PVAL2) promotes osteogenesis, while the random addition of short‐chapped fibers (PVAS) facilitate tenogenic differentiation. As a consequence of the findings, fiber placement is crucial to the mechanical properties of composite hydrogels that ultimately control musculoskeletal differentiation signals through mechanosensing pathways.

Orchiectomy sensitizes cortical bone in male mice to the harmful effects of kynurenine

Kynurenine (Kyn) is a tryptophan metabolite that increases with age and promotes musculoskeletal dysfunction. We previously found a sexually dimorphic pattern in how Kyn affects bone, with harmful effects more prevalent in females than males. This raises the possibility that male sex steroids might exert a protective effect that blunts the effects of Kyn in males. To test this, orchiectomy (ORX) or sham surgeries were performed on 6-month-old C57BL/6 mice, after which mice received Kyn (10 mg/kg) or vehicle via intraperitoneal injection, once daily, 5×/week, for four weeks. Bone histomorphometry, DXA, microCT, and serum marker analyses were performed after sacrifice. In vitro studies were performed to specifically test the effect of testosterone on activation of aryl hydrocarbon receptor (AhR)-mediated signaling by Kyn in mesenchymal-lineage cells. Kyn treatment reduced cortical bone mass in ORX- but not sham-operated mice. Trabecular bone was unaffected. Kyn's effects on cortical bone in ORX mice were attributed primarily to enhanced endosteal bone resorption activity. Bone marrow adipose tissue was increased in Kyn-treated ORX animals but was unchanged by Kyn in sham-operated mice. ORX surgery increased mRNA expression of the aryl hydrocarbon receptor (AhR) and its target gene Cyp1a1 in the bone, suggesting a priming and/or amplification of AhR signaling pathways. Mechanistic in vitro studies revealed that testosterone blunted Kyn-stimulated AhR transcriptional activity and Cyp1a1 expression in mesenchymal-linage cells. These data suggest a protective role for male sex steroids in blunting the harmful effects of Kyn in cortical bone. Therefore, testosterone may play an important role in regulating Kyn/AhR signaling in musculoskeletal tissues, suggesting crosstalk between male sex steroids and Kyn signaling may influence age-associated musculoskeletal frailty.

Combined hormonal contraceptive use is not protective against musculoskeletal conditions or injuries: a systematic review with data from 5 million females

ObjectiveAssess the association between combined hormonal contraceptives (CHC) use and musculoskeletal tissue pathophysiology, injuries or conditions.DesignSystematic review with semiquantitative analyses and certainty of evidence assessment, guided by the Grading of...

Accuracy of Time to Treatment Initiation Data in Musculoskeletal Soft Tissue Sarcoma.

Time to treatment initiation (TTI) is a quality metric in cancer care. The purpose of this study is to determine the accuracy of TTI data from a single cancer center registry that reports to the National Cancer Database (NCDB) for sarcoma diagnoses. A retrospective analysis of a single Commission on Cancer (CoC)-accredited cancer center's tumor registry between 2006 and 2016 identified 402 patients who underwent treatment of a musculoskeletal soft tissue sarcoma and had TTI data available. Registry-reported TTI was extracted from the tumor registry. Effective TTI was manually calculated by medical record review as the number of days from the date of tissue diagnosis to initiation of first effective treatment. Effective treatment was defined as oncologic surgical excision or initiation of radiation therapy or chemotherapy. Registry-reported TTI and effective TTI values were compared for concordance in all patients. In the entire cohort, 25% (99/402) of patients had TTI data discordance, all related to surgical treatment definition. For patients with a registry-reported value of TTI = 0 days, 74% (87/118) had a diagnostic surgical procedure coded as their first treatment event, with 73 unplanned incomplete excision procedures and 14 incisional biopsies. In these patients, effective TTI was on average 59 days (P < 0.001). For patients with a registry-reported value of TTI >0 days, only 4% (12/284) had discordant TTI values. Nearly three-fourths of patients with a registry-reported value of TTI = 0 days in a large, CoC-accredited cancer center registry had a diagnostic procedure coded as their first treatment event, though their effective treatment had not yet started. These data suggest that TTI is likely longer than what is reported to the NCDB. Redefinition of what constitutes surgical treatment should be considered to improve the accuracy of data used in measuring TTI in sarcoma.

Androgen receptor coordinates muscle metabolic and contractile functions.

Androgens are anabolic steroid hormones that exert their function by binding to the androgen receptor (AR). We have previously established that AR deficiency in limb muscles impairs sarcomere myofibrillar organization and decreases muscle strength in male mice. However, despite numerous studies performed in men and rodents, the signalling pathways controlled by androgens via their receptor in skeletal muscles remain poorly understood. Male ARskm-/y (n=7-12) and female ARskm-/- mice (n=9), in which AR is selectively ablated in myofibres of musculoskeletal tissue, and male AR(i)skm-/y , in which AR is selectively ablated in post-mitotic skeletal muscle myofibres (n=6), were generated. Longitudinal monitoring of body weight, blood glucose, insulin, lipids and lipoproteins was performed, alongside metabolomic analyses. Glucose metabolism was evaluated in C2C12 cells treated with 5α-dihydrotestosterone (DHT) and the anti-androgen flutamide (n=6). Histological analyses on macroscopic and ultrastructural levels of longitudinal and transversal muscle sections were conducted. The transcriptome of gastrocnemius muscles from control and ARskm-/y mice was analysed at the age of 9weeks (P<0.05, 2138 differentially expressed genes) and validated by RT-qPCR analysis. The AR (4691 peaks with false discovery rate [FDR]<0.1) and H3K4me2 (47225 peaks with FDR<0.05) cistromes in limb muscles were determined in 11-week-old wild-type mice. We show that disrupting the androgen/AR axis impairs in vivo glycolytic activity and fastens the development of type 2 diabetes in male, but not in female mice. In agreement, treatment with DHT increases glycolysis in C2C12 myotubes by 30%, whereas flutamide has an opposite effect. Fatty acids are less efficiently metabolized in skeletal muscles of ARskm-/y mice and accumulate in cytoplasm, despite increased transcript levels of genes encoding key enzymes of beta-oxidation and mitochondrial content. Impaired glucose and fatty acid metabolism in AR-deficient muscle fibres is associated with 30% increased lysine and branched-chain amino acid catabolism, decreased polyamine biosynthesis and disrupted glutamate transamination. This metabolic switch generates ammonia (2-fold increase) and oxidative stress (30% increased H2 O2 levels), which impacts mitochondrial functions and causes necrosis in <1% fibres. We unravel that AR directly activates the transcription of genes involved in glycolysis, oxidative metabolism and muscle contraction. Our study provides important insights into diseases caused by impaired AR function in musculoskeletal system and delivers a deeper understanding of skeletal muscle pathophysiological dynamics that is instrumental to develop effective treatment for muscle disorders.

The effects of the exposure of musculoskeletal tissue to extracorporeal shock waves

Breaking the capacity barrier in intercalation-type anode materials for lithium-ion batteries while preserving other essential electrochemical properties remains a significant challenge. Here, using perovskite SrVO3 as a model, we demonstrate the feasibility of employing defect engineering to provide extra active sites for electrochemical reactions. Defective SrxVO3-δ samples with a unique amorphous-crystalline dual-phase structure are successfully prepared by regulating the nonstoichiometric Sr/V ratio and using a non-equilibrium solution combustion strategy to alleviate nucleation. The dual-phase SrxVO3-δ electrodes, which take advantage of both the high defect concentration advantage of amorphous and the high electrical/ionic conductivity of crystalline, give a high specific capacity of 508 mAh/g at a safe potential of 1.0 V vs. Li/Li+, showing a 40% increase over SrVO3 electrodes and outperforming most state-of-the-art intercalation-based anodes. In addition, when coupling with LiFePO4 cathode, the SrxVO3-δ electrodes can operate over 10,000 cycles with 91% capacity retention, overcoming the limited structural stability exhibited in typical defective electrodes. The study demonstrates the viability of modulating the crystallinity in intercalation-based anodes to enhance electrochemical performance and paves the way for the advancement of Li-ion battery technology.

Advanced silk materials for musculoskeletal tissue regeneration.

Musculoskeletal diseases are the leading causes of chronic pain and physical disability, affecting millions of individuals worldwide. Over the past two decades, significant progress has been made in the field of bone and cartilage tissue engineering to combat the limitations of conventional treatments. Among various materials used in musculoskeletal tissue regeneration, silk biomaterials exhibit unique mechanical robustness, versatility, favorable biocompatibility, and tunable biodegradation rate. As silk is an easy-to-process biopolymer, silks have been reformed into various materials formats using advanced bio-fabrication technology for the design of cell niches. Silk proteins also offer active sites for chemical modifications to facilitate musculoskeletal system regeneration. With the emergence of genetic engineering techniques, silk proteins have been further optimized from the molecular level with other functional motifs to introduce new advantageous biological properties. In this review, we highlight the frontiers in engineering natural and recombinant silk biomaterials, as well as recent progress in the applications of these new silks in the field of bone and cartilage regeneration. The future potentials and challenges of silk biomaterials in musculoskeletal tissue engineering are also discussed. This review brings together perspectives from different fields and provides insight into improved musculoskeletal engineering.

An ERK-dependent molecular switch antagonizes fibrosis and promotes regeneration in spiny mice (Acomys).

Although most mammals heal injured tissues and organs with scarring, spiny mice (Acomys) naturally regenerate skin and complex musculoskeletal tissues. Now, the core signaling pathways driving mammalian tissue regeneration are poorly characterized. Here, we show that, while immediate extracellular signal-regulated kinase (ERK) activation is a shared feature of scarring (Mus) and regenerating (Acomys) injuries, ERK activity is only sustained at high levels during complex tissue regeneration. Following ERK inhibition, ear punch regeneration in Acomys shifted toward fibrotic repair. Using single-cell RNA sequencing, we identified ERK-responsive cell types. Loss- and gain-of-function experiments prompted us to uncover fibroblast growth factor and ErbB signaling as upstream ERK regulators of regeneration. The ectopic activation of ERK in scar-prone injuries induced a pro-regenerative response, including cell proliferation, extracellular matrix remodeling, and hair follicle neogenesis. Our data detail an important distinction in ERK activity between regenerating and poorly regenerating adult mammals and open avenues to redirect fibrotic repair toward regenerative healing.

Piezoelectric Nanomaterials Activated by Ultrasound in Disease Treatment.

Electric stimulation has been used in changing the morphology, status, membrane permeability, and life cycle of cells to treat certain diseases such as trauma, degenerative disease, tumor, and infection. To minimize the side effects of invasive electric stimulation, recent studies attempt to apply ultrasound to control the piezoelectric effect of nano piezoelectric material. This method not only generates an electric field but also utilizes the benefits of ultrasound such as non-invasive and mechanical effects. In this review, important elements in the system, piezoelectricity nanomaterial and ultrasound, are first analyzed. Then, we summarize recent studies categorized into five kinds, nervous system diseases treatment, musculoskeletal tissues treatment, cancer treatment, anti-bacteria therapy, and others, to prove two main mechanics under activated piezoelectricity: one is biological change on a cellular level, the other is a piezo-chemical reaction. However, there are still technical problems to be solved and regulation processes to be completed before widespread use. The core problems include how to accurately measure piezoelectricity properties, how to concisely control electricity release through complex energy transfer processes, and a deeper understanding of related bioeffects. If these problems are conquered in the future, piezoelectric nanomaterials activated by ultrasound will provide a new pathway and realize application in disease treatment.

Extended Application of Inertial Measurement Units in Biomechanics: From Activity Recognition to Force Estimation.

Abnormal posture or movement is generally the indicator of musculoskeletal injuries or diseases. Mechanical forces dominate the injury and recovery processes of musculoskeletal tissue. Using kinematic data collected from wearable sensors (notably IMUs) as input, activity recognition and musculoskeletal force (typically represented by ground reaction force, joint force/torque, and muscle activity/force) estimation approaches based on machine learning models have demonstrated their superior accuracy. The purpose of the present study is to summarize recent achievements in the application of IMUs in biomechanics, with an emphasis on activity recognition and mechanical force estimation. The methodology adopted in such applications, including data pre-processing, noise suppression, classification models, force/torque estimation models, and the corresponding application effects, are reviewed. The extent of the applications of IMUs in daily activity assessment, posture assessment, disease diagnosis, rehabilitation, and exoskeleton control strategy development are illustrated and discussed. More importantly, the technical feasibility and application opportunities of musculoskeletal force prediction using IMU-based wearable devices are indicated and highlighted. With the development and application of novel adaptive networks and deep learning models, the accurate estimation of musculoskeletal forces can become a research field worthy of further attention.

Engineered Highly Porous Polyvinyl Alcohol Hydrogels with Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and Graphene Nanosheets for Musculoskeletal Tissue Engineering: Morphology, Water Sorption, Thermal, Mechanical, Electrical Properties, and Biocompatibility.

Electroactive composite materials are very promising for musculoskeletal tissue engineering because they can be applied in combination with electrostimulation. In this context, novel graphene-based poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/polyvinyl alcohol (PHBV/PVA) semi-interpenetrated networks (semi-IPN) hydrogels were engineered with low amounts of graphene (G) nanosheets dispersed within the polymer matrix to endow them with electroactive properties. The nanohybrid hydrogels, obtained by applying a hybrid solvent casting-freeze-drying method, show an interconnected porous structure and a high water-absorption capacity (swelling degree > 1200%). The thermal characterization indicates that the structure presents microphase separation, with PHBV microdomains located between the PVA network. The PHBV chains located in the microdomains are able to crystallize; even more after the addition of G nanosheets, which act as a nucleating agent. Thermogravimetric analysis indicates that the degradation profile of the semi-IPN is located between those of the neat components, with an improved thermal stability at high temperatures (>450 °C) after the addition of G nanosheets. The mechanical (complex modulus) and electrical properties (surface conductivity) significantly increase in the nanohybrid hydrogels with 0.2% of G nanosheets. Nevertheless, when the amount of G nanoparticles increases fourfold (0.8%), the mechanical properties diminish and the electrical conductivity does not increase proportionally, suggesting the presence of G aggregates. The biological assessment (C2C12 murine myoblasts) indicates a good biocompatibility and proliferative behavior. These results reveal a new conductive and biocompatible semi-IPN with remarkable values of electrical conductivity and ability to induce myoblast proliferation, indicating its great potential for musculoskeletal tissue engineering.

3D Printing of Bone Substitutes Based on Vat Photopolymerization Processes: A Systematic Review

Treatment options for critically sized bone defects are currently limited to metal osteosynthesis, autologous bone grafting, or calcium-based implants to bridge the gap. Additive manufacturing techniques pose a possible alternative. The light-basedthree-dimensional printing process of vat photopolymerization (VP) is of particular interest since it enables the printing of complex scaffold architectures at high resolution. This review compares multiple vat photopolymerization processes as well as the employed resin components’ interactions with musculoskeletal cells and tissue. The results show an outstanding printing capability, exceeding the potential of other printing methods. However, despite the availability of various biocompatible materials, neither the mechanical strength of bone nor the scale necessary for clinical application has been achieved so far when relying on single material constructs. One possible solution is the development of adaptive hybrid constructs produced with multimaterial VP.

Engineering Cell-ECM-Material Interactions for Musculoskeletal Regeneration.

The extracellular microenvironment regulates many of the mechanical and biochemical cues that direct musculoskeletal development and are involved in musculoskeletal disease. The extracellular matrix (ECM) is a main component of this microenvironment. Tissue engineered approaches towards regenerating muscle, cartilage, tendon, and bone target the ECM because it supplies critical signals for regenerating musculoskeletal tissues. Engineered ECM-material scaffolds that mimic key mechanical and biochemical components of the ECM are of particular interest in musculoskeletal tissue engineering. Such materials are biocompatible, can be fabricated to have desirable mechanical and biochemical properties, and can be further chemically or genetically modified to support cell differentiation or halt degenerative disease progression. In this review, we survey how engineered approaches using natural and ECM-derived materials and scaffold systems can harness the unique characteristics of the ECM to support musculoskeletal tissue regeneration, with a focus on skeletal muscle, cartilage, tendon, and bone. We summarize the strengths of current approaches and look towards a future of materials and culture systems with engineered and highly tailored cell-ECM-material interactions to drive musculoskeletal tissue restoration. The works highlighted in this review strongly support the continued exploration of ECM and other engineered materials as tools to control cell fate and make large-scale musculoskeletal regeneration a reality.

A Stretchable Strain Sensor System for Wireless Measurement of Musculoskeletal Soft Tissue Strains

AbstractMeasurement of in vivo strain patterns of musculoskeletal soft tissues (MSTs) during functional activities reveals their biomechanical function, supports the identification and understanding of pathologies, and quantifies tissue adaptation during healing. These scientific and clinical insights have motivated the development and application of various strain sensors to quantify MST strains in either intraoperative or dynamic in vivo conditions. In this study, a strain sensor system is developed based on stretchable electronics and radio frequency identification technologies. In this system, a flexible inductor‐capacitor‐resistor sensor is fabricated such that it can be wirelessly excited by a custom‐designed readout box through electronic resonance. The resonant frequency of the sensor changes when the capacitor is stretched, which is then also recorded by the readout box at a sampling rate of 1024 Hz. Suturing the stretchable capacitor onto the MST allows it to be stretched in line with musculoskeletal deformations, hence providing an indirect method to assess strain patterns in vivo. Application of the system ex vivo indicates that the signal remains linear between 0 and 25% strain and is electronically stable in a simulated in vivo environment for one week and over 100 000 cycles of fatigue loadings. The strain sensor exhibits excellent resolution (0.1% strain, ≈9 µm) during wireless strain measurement. Finally, sensor implantation and strain measurement onto the medial gastrocnemius tendon of a sheep indicate that the sensor is able to record repetitive strain patterns in vivo during dynamic movements. This study indicates the potential scientific and clinical applicability in vivo.

Ca2+-Activated K+ Channels in Progenitor Cells of Musculoskeletal Tissues: A Narrative Review.

Musculoskeletal disorders represent one of the main causes of disability worldwide, and their prevalence is predicted to increase in the coming decades. Stem cell therapy may be a promising option for the treatment of some of the musculoskeletal diseases. Although significant progress has been made in musculoskeletal stem cell research, osteoarthritis, the most-common musculoskeletal disorder, still lacks curative treatment. To fine-tune stem-cell-based therapy, it is necessary to focus on the underlying biological mechanisms. Ion channels and the bioelectric signals they generate control the proliferation, differentiation, and migration of musculoskeletal progenitor cells. Calcium- and voltage-activated potassium (KCa) channels are key players in cell physiology in cells of the musculoskeletal system. This review article focused on the big conductance (BK) KCa channels. The regulatory function of BK channels requires interactions with diverse sets of proteins that have different functions in tissue-resident stem cells. In this narrative review article, we discuss the main ion channels of musculoskeletal stem cells, with a focus on calcium-dependent potassium channels, especially on the large conductance BK channel. We review their expression and function in progenitor cell proliferation, differentiation, and migration and highlight gaps in current knowledge on their involvement in musculoskeletal diseases.

Abstract 932: Snapshot! Exploring sample diversity of sarcoma cancers across common data repositories

Abstract Sarcoma is a cancer which originates in the body's connective tissues of mesenchymal origin. These are tissues like bones and muscles that support or protect other parts of the body. About ~16,000 sarcomas are diagnosed annually in the US, with ~6,700 deaths attributed to the disease. Sarcomas are typically divided into two major groups: bone sarcomas and soft-tissue sarcomas, each of which has multiple subtypes. However, because of their diversity in site-of-origin, sarcomas vary greatly in their presentation and histological features. Based on The World Health Organization’s (WHO) current classification system that categorizes musculoskeletal soft tissue tumours (STT) and bone tissue tumours, there are 50+ subtypes of sarcoma recognized today. Unsurprisingly, given the relative rarity of sarcoma type tumors, sample procurement has proved a challenge for the field. Consequently, there currently exist major gaps in our understanding of the genetic and molecular hallmarks of various sarcoma subtypes. Here we examine the sample and subtype classifications of sarcoma across some of the major DNA sequencing studies and data repositories to provide an overview of the available sample space. We highlight areas where the sample procurement is lagging and discuss subtypes that are missing all-together. Inclusion of some of the major genomic correlates showcases some of the similarities shared by these sequencing efforts, while emphasizing key genetic differences between subtypes. This work provides a clear roadmap for clinicians on how to best prioritize future sarcoma sample procurement and sequencing. Citation Format: Alfredo Enrique Gonzalez, Yash Patel, Chenghao Zhu, Takafumi N. Yamaguchi, Mao Tian, Sarah Hiyari, Ahmad A. Shihabi, Stefan Eng, Helena Winata, Jaron Arbert, Arpi Beshlikyan, Ardalan Davarifar, Alice Soragni, Paul C. Boutros. Snapshot! Exploring sample diversity of sarcoma cancers across common data repositories [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 932.

How controlled motion alters the biophysical properties of musculoskeletal tissue architecture

IntroductionMovement is fundamental to the normal behaviour of the hand, not only for day-to-day activity, but also for fundamental processes like development, tissue homeostasis and repair. Controlled motion is a concept that hand therapists apply to their patients daily for functional gains, yet the scientific understanding of how this works is poorly understood. Purpose of the articleTo review the biology of the tissues in the hand that respond to movement and provide a basic science understanding of how it can be manipulated to facilitate better functionThe review outlines the concept of controlled motion and actions across the scales of tissue architecture, highlighting the the role of movement forces in tissue development, homeostasis and repair. The biophysical behaviour of mechanosensitve tissues of the hand such as skin, tendon, bone and cartilage are discussed. ConclusionControlled motion during early healing is a form of controlled stress and can be harnessed to generate appropriate reparative tissues. Understanding the temporal and spatial biology of tissue repair allows therapists to tailor therapies that allow optimal recovery based around progressive biophysical stimuli by movement.