Vennila Suriyagandhi , Ying Ma , Veronica Paparozzi , Tiziana Guarnieri , Biagio Di Pietro , Giovanna Maria Dimitri , Paolo Tieri , Claudia Sala , Darong Lai , Christine Nardini
{"title":"Mechanotransduction and inflammation: An updated comprehensive representation","authors":"Vennila Suriyagandhi , Ying Ma , Veronica Paparozzi , Tiziana Guarnieri , Biagio Di Pietro , Giovanna Maria Dimitri , Paolo Tieri , Claudia Sala , Darong Lai , Christine Nardini","doi":"10.1016/j.mbm.2024.100112","DOIUrl":"10.1016/j.mbm.2024.100112","url":null,"abstract":"<div><div>Mechanotransduction is the process that enables the conversion of mechanical cues into biochemical signaling. While all our cells are well known to be sensitive to such stimuli, the details of the systemic interaction between mechanical input and inflammation are not well integrated. Often, indeed, they are considered and studied in relatively compartmentalized areas, and we therefore argue here that to understand the relationship of mechanical stimuli with inflammation – with a high translational potential - it is crucial to offer and analyze a unified view of mechanotransduction. We therefore present here pathway representation, recollected with the standard systems biology markup language (SBML) and explored with network biology approaches, offering RAC1 as an exemplar and emerging molecule with potential for medical translation.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 1","pages":"Article 100112"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143165421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hanxiao Chen , Chengxiu Peng , Fei Fang , Yuhao Li , Xiaran Liu , Ying Hu , Guixue Wang , Xiaoheng Liu , Yang Shen
{"title":"Angiogenesis within atherosclerotic plaques: Mechanical regulation, molecular mechanism and clinical diagnosis","authors":"Hanxiao Chen , Chengxiu Peng , Fei Fang , Yuhao Li , Xiaran Liu , Ying Hu , Guixue Wang , Xiaoheng Liu , Yang Shen","doi":"10.1016/j.mbm.2025.100114","DOIUrl":"10.1016/j.mbm.2025.100114","url":null,"abstract":"<div><div>Atherosclerosis (AS) is a disease characterized by focal cholesterol accumulation and insoluble inflammation in arterial intima, leading to the formation of an atherosclerotic plaque consisting of lipids, cells, and fibrous matrix. The presence of plaque can restrict or obstruct blood flow, resulting in arterial stenosis and local mechanical microenvironment changes including flow shear stress, vascular matrix stiffness, and plaque structural stress. Neovascularization within the atherosclerotic plaque plays a crucial role in both plaque growth and destabilization, potentially leading to plaque rupture and fatal embolism. However, the exact interactions between neovessels and plaque remain unclear. In this review, we provide a comprehensive analysis of the origin of intraplaque neovessels, the contributing factors, underlying molecular mechanisms, and associated signaling pathways. We specifically emphasize the role of mechanical factors contributing to angiogenesis in atherosclerotic plaques. Additionally, we summarize the imaging techniques and therapeutic strategies for intraplaque neovessels to enhance our understanding of this field.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 1","pages":"Article 100114"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143428126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chunhua Liao , Jing Liu , Shuanglong Hou , Wendong Zhang , Xin Zhao , Zhipan Hou , Honglei Quan , Zhaohui Tian , Rui Liu , Yuting Zhao
{"title":"Relationship between bilateral symmetry of foot posture and lower limb musculoskeletal injuries among workers engaged in physically demanding occupations: A cross-sectional investigation","authors":"Chunhua Liao , Jing Liu , Shuanglong Hou , Wendong Zhang , Xin Zhao , Zhipan Hou , Honglei Quan , Zhaohui Tian , Rui Liu , Yuting Zhao","doi":"10.1016/j.mbm.2024.100098","DOIUrl":"10.1016/j.mbm.2024.100098","url":null,"abstract":"<div><div>Even though the link between foot posture and lower-extremity injuries remains controversial, there has been little research focus on bilateral foot symmetry. This study evaluated the correlation between bilateral symmetry in foot posture and lower extremity musculoskeletal injuries among workers in physically intensive occupations. A total of 248 participants with physically demanding roles were enrolled. Historical data on lower-limb musculoskeletal injuries were obtained through a review of medical records, supplemented by results from on-site consultations. The foot arch index (AI) was quantitatively measured using a 3D laser foot scanner, and foot posture was evaluated using the foot posture index-6 (FPI-6). The participants were categorized into subgroups based on bilateral symmetry assessments of their feet. Logistic regression analyses were performed for statistical comparisons after adjusting for potential confounding factors. The results indicate that abnormalities in foot posture and arch, assessed using the FPI-6 and AI, were identified in 42.3 % and 47.2 % of participants, respectively, with 20.9 % and 16.5 % demonstrating bilateral asymmetry in these parameters. When comparing bilateral and unilateral foot protonation with bilaterally normal feet, the risk adjustments revealed differences of 2.274 (95 % CI: 1.094–4.729, <em>P</em> = 0.028) and 2.751 (95 % CI: 1.222–6.191, <em>P</em> = 0.015), respectively. Furthermore, the risk adjustment for age, BMI, smoking status, physical training years, training time, training frequency, warm-up before training, relaxation after training, MIS prevention, and treatment learning for unilateral flatfoot relative to bilateral normal feet was 3.197 (95 % CI:1.235–8.279, <em>P</em> = 0.017). This study demonstrates that workers in physically demanding occupations who exhibit unilateral foot protonation or unilateral flatfoot are at an increased risk of lower-extremity musculoskeletal injuries.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 1","pages":"Article 100098"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142534805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexander M. Regner , Maximilien DeLeon , Kalin D. Gibbons , Sean Howard , Derek Q. Nesbitt , Seyedeh F. Darghiasi , Anamaria G. Zavala , Trevor J. Lujan , Clare K. Fitzpatrick , Mary C. Farach-Carson , Danielle Wu , Gunes Uzer
{"title":"Increased deformations are dispensable for encapsulated cell mechanoresponse in engineered bone analogs mimicking aging bone marrow","authors":"Alexander M. Regner , Maximilien DeLeon , Kalin D. Gibbons , Sean Howard , Derek Q. Nesbitt , Seyedeh F. Darghiasi , Anamaria G. Zavala , Trevor J. Lujan , Clare K. Fitzpatrick , Mary C. Farach-Carson , Danielle Wu , Gunes Uzer","doi":"10.1016/j.mbm.2024.100097","DOIUrl":"10.1016/j.mbm.2024.100097","url":null,"abstract":"<div><div>Aged individuals and astronauts experience bone loss despite rigorous physical activity. Bone mechanoresponse is in-part regulated by mesenchymal stem cells (MSCs) that respond to mechanical stimuli. Direct delivery of low intensity vibration (LIV) recovers MSC proliferation in senescence and simulated microgravity models, indicating that age-related reductions in mechanical signal delivery within bone marrow may contribute to declining bone mechanoresponse. To answer this question, we developed a 3D bone marrow analog that controls trabecular geometry, marrow mechanics and external stimuli. Validated finite element (FE) models were developed to quantify strain environment within hydrogels during LIV. Bone marrow analogs with gyroid-based trabeculae of scaffold volume fractions (SV/TV) corresponding to adult (25 %) and aged (13 %) mice were printed using polylactic acid (PLA). MSCs encapsulated in migration-permissive hydrogels within printed trabeculae showed robust cell populations on both PLA surface and hydrogel within a week. Following 14 days of LIV treatment (1 g, 100 Hz, 1 h/day), cell proliferation, type-I collagen (Collagen-I) and filamentous actin (F-actin) were quantified for the cells in the hydrogel fraction. While LIV increased all measured outcomes, FE models predicted higher von Mises strains for the 13 % SV/TV groups (0.2 %) when compared to the 25 % SV/TV group (0.1 %). While LIV increased collagen-I volume 34 % more in 13 % SV/TV groups when compared to 25 % SV/TV groups, collagen-I and F-actin measures remained lower in the 13 % SV/TV groups when compared to 25 % SV/TV counterparts, indicating that both LIV-induced strains and scaffold volume fraction (i.e. available scaffold surface) affect cell behavior in the hydrogel phase. Overall, bone marrow analogs offer a robust and repeatable platform to study bone mechanobiology.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 1","pages":"Article 100097"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142534799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The first embryo, the origin of cancer and animal phylogeny. V. Cancer stem cells as the unifying biomechanical principle between embryology and oncology","authors":"Jaime Cofre","doi":"10.1016/j.mbm.2024.100110","DOIUrl":"10.1016/j.mbm.2024.100110","url":null,"abstract":"<div><div>The role of embryology in metazoan evolution is rooted deeply in the history of science. Viewing Neoplasia as an evolutionary engine provides a scientific basis for reexamining the disease cancer. Once the embryo is understood as a benign tumor with a pivotal role in the evolution of all animal forms, there will be an immediate paradigm shift in the search for cancer cure, potentially revealing insights that may be buried within the great developmental transitions of metazoans. This article discusses one of the unifying principles between embryology and oncology, namely cancer stem cells. Some considerations are also provided on the central role of physics and biomechanics in the assembly of the first embryo, which can be regarded as a differentiated benign tumor. Mechanical impregnation of the nucleus of a stem cell, culminating in a totipotent/multipotent cell, was a major event safeguarding the success of embryogenesis throughout evolution. Germ cells in the earliest ctenophore embryos underwent delayed differentiation, subsequent to the mechanical assembly of the embryo. Finally, a discussion is presented on the concept that cancer and embryogenesis (cancer and healthy stem cells) are two sides of the same coin, that is, of the same process. The only difference is that cancer stem cells reveal themselves in inappropriate contexts. Neoplasia is a free force, whereas cancer is a force contained by animal organization.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 1","pages":"Article 100110"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143165420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anneke S.K. Verbruggen , Elan C. McCarthy , Roisin M. Dwyer , Laoise M. McNamara
{"title":"Mechanobiological cues to bone cells during early metastasis drive later osteolysis: A computational mechanoregulation framework prediction","authors":"Anneke S.K. Verbruggen , Elan C. McCarthy , Roisin M. Dwyer , Laoise M. McNamara","doi":"10.1016/j.mbm.2024.100100","DOIUrl":"10.1016/j.mbm.2024.100100","url":null,"abstract":"<div><div>Bone cells contribute to tumour metastasis by producing biochemical factors that stimulate tumour cell homing and proliferation, but also by resorbing bone matrix (osteolysis) that releases further stimulatory factors for tumour growth in a vicious cycle. Changes in the local mechanical environment of bone tissue occur during early metastasis, which might activate mechanobiological responses by resident bone cells (osteocytes) to activate resorption (osteoclasts) and thereby contribute to tumour invasion. The objective of this study is to investigate whether bone osteolysis is driven by early changes in the bone mechanical environment during metastasis by (a) implementing subject-specific FE models of metastatic femora to predict the mechanical environment within bone tissue during early metastasis (3-weeks after tumour inoculation) and then (b) applying mechanoregulation theory to predict bone tissue remodelling as a function of the evolving mechanical environment within bone tissue during breast cancer-bone metastasis. We implemented a global resorption rate derived from an experimental model, but the mechanoregulation algorithm predicted localised bone loss in the greater trochanter region, the same region where osteolysis was prevalent after three weeks of metastasis development in the animal model. Moreover, the mechanical environment evolved in a similar manner to that reported in separate subject-specific finite element models of these same animals by 6 weeks. Thus, we propose that early changes in the physical environment of bone tissue during metastasis may elicit mechanobiological cues for bone cells and activate later osteolytic bone destruction.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 1","pages":"Article 100100"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143165419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sara J. Olsen , Rose E. Leader , Abigail L. Mortimer , Bethany Almeida
{"title":"Matrix stiffness and viscoelasticity influence human mesenchymal stem cell immunomodulation","authors":"Sara J. Olsen , Rose E. Leader , Abigail L. Mortimer , Bethany Almeida","doi":"10.1016/j.mbm.2024.100111","DOIUrl":"10.1016/j.mbm.2024.100111","url":null,"abstract":"<div><div>Human mesenchymal stem cells (hMSCs) have immense wound healing potential due to their immunomodulatory behavior. To control this behavior and reduce heterogeneity, researchers look to biomaterials, as matrix stiffness and viscoelasticity have been shown to control hMSC immunomodulation. However, the understanding of the effects of these biophysical cues on hMSC immunomodulation remains limited; a broad study investigating the potentially synergistic effects of matrix stiffness and viscoelasticity on hMSC immunomodulation is needed in order to support future work developing biomaterials for hMSC wound healing applications. We developed polyacrylamide (PAAm) gels with varying matrix stiffnesses with or without a viscoelastic element and explored the effects of these on hMSC-matrix interactions and immunomodulatory cytokine expression in both a normal growth media and an immunomodulatory growth media mimetic of a chronic, non-healing wound. Expression of IL-10, VEGF, and PGE<sub>2</sub> were upregulated in immunomodulatory growth media over normal growth media, demonstrating the synergistic effects of biochemical signaling on hMSC immunomodulatory behavior. In addition, the addition of a viscoelastic element had both inhibitory and accentuating effects based on the cytokine and biochemical signaling in the cell culture media. Overall, this study provides a broad perspective on the immunomodulatory behavior of hMSCs due to stiffness and viscoelasticity.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 1","pages":"Article 100111"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143165418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ultrasound imaging and regulated mechanotransduction for characteristics, regeneration, and therapeutics of bone","authors":"Yi-Xian Qin","doi":"10.1016/j.mbm.2025.100116","DOIUrl":"10.1016/j.mbm.2025.100116","url":null,"abstract":"<div><div>Ultrasound imaging has been widely used in clinical diagnoses, such as B-mode and M-mode ultrasound imaging for cardiovascular, abdomen, OB-Gyn, and other soft tissue and organs in clinical diagnoses. Ultrasound imaging has traditionally been limited in its application to bone because of the high acoustic impedance and density of trabecular and cortical bone structure and density alterations, high wave reflection, absorption, scattering, and low penetration, which result in significant reflection and attenuation of ultrasonic energy in such mineral tissues. Recent advancements in quantitative ultrasound technology have opened new possibilities for noninvasive characteristics of bone quality through transmitted or backscattered signals, offering a radiation-free alternative to traditional imaging modalities like dual-energy X-ray absorptiometry (DEX), X-rays, and CT scans. In addition, low-intensity ultrasound (LIUS) has been studied and applied to promote bone regeneration and fracture healing through induced mechanotransduction in tissue and cells. The field of bone ultrasound encompasses fundamental research on the interaction of elastic waves with cortical and trabecular bone microstructures, the development of innovative imaging methodologies and medical applications such as bone health assessment for osteoporosis diagnosis, therapeutic use of LIUS, and phase aberration correction inside the skull. This work has highlighted recent developments and advancements in ultrasound diagnosis and therapeutics, induced cellular and molecular pathways, and future directions using ultrasound as a promising imaging tool and treatment method.</div></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"3 1","pages":"Article 100116"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143480292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhiqiang Liu, Si Da Ling, Kaini Liang, Yihan Chen, Yudi Niu, Lei Sun, Junyang Li, Yanan Du
{"title":"Viscoelasticity of ECM and cells—origin, measurement and correlation","authors":"Zhiqiang Liu, Si Da Ling, Kaini Liang, Yihan Chen, Yudi Niu, Lei Sun, Junyang Li, Yanan Du","doi":"10.1016/j.mbm.2024.100082","DOIUrl":"10.1016/j.mbm.2024.100082","url":null,"abstract":"<div><p>The extracellular matrix (ECM) and cells are crucial components of natural tissue microenvironments, and they both demonstrate dynamic mechanical properties, particularly viscoelastic behaviors, when exposed to external stress or strain over time. The capacity to modify the mechanical properties of cells and ECM is crucial for gaining insight into the development, physiology, and pathophysiology of living organisms. As an illustration, researchers have developed hydrogels with diverse compositions to mimic the properties of the native ECM and use them as substrates for cell culture. The behavior of cultured cells can be regulated by modifying the viscoelasticity of hydrogels. Moreover, there is widespread interest across disciplines in accurately measuring the mechanical properties of cells and the surrounding ECM, as well as exploring the interactive relationship between these components. Nevertheless, the lack of standardized experimental methods, conditions, and other variables has hindered systematic comparisons and summaries of research findings on ECM and cell viscoelasticity. In this review, we delve into the origins of ECM and cell viscoelasticity, examine recently developed methods for measuring ECM and cell viscoelasticity, and summarize the potential interactions between cell and ECM viscoelasticity. Recent research has shown that both ECM and cell viscoelasticity experience alterations during in vivo pathogenesis, indicating the potential use of tailored viscoelastic ECM and cells in regenerative medicine.</p></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"2 4","pages":"Article 100082"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949907024000457/pdfft?md5=d6a24f3aa25c8acf54e6bcfd62d47df9&pid=1-s2.0-S2949907024000457-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142058276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
David Gothard , Michael Rotherham , Emma L. Smith , Janos M. Kanczler , James Henstock , Julia A. Wells , Carol A. Roberts , Omar Qutachi , Heather Peto , Hassan Rashidi , Luis Rojo , Lisa J. White , Molly M. Stevens , Alicia J. El Haj , Felicity R.A.J. Rose , Richard O.C. Oreffo
{"title":"In vivo analysis of hybrid hydrogels containing dual growth factor combinations, and skeletal stem cells under mechanical stimulation for bone repair","authors":"David Gothard , Michael Rotherham , Emma L. Smith , Janos M. Kanczler , James Henstock , Julia A. Wells , Carol A. Roberts , Omar Qutachi , Heather Peto , Hassan Rashidi , Luis Rojo , Lisa J. White , Molly M. Stevens , Alicia J. El Haj , Felicity R.A.J. Rose , Richard O.C. Oreffo","doi":"10.1016/j.mbm.2024.100096","DOIUrl":"10.1016/j.mbm.2024.100096","url":null,"abstract":"<div><p>Bone tissue engineering requires a combination of materials, cells, growth factors and mechanical cues to recapitulate bone formation. In this study we evaluated hybrid hydrogels for minimally invasive bone formation by combining biomaterials with skeletal stem cells and staged release of growth factors together with mechanotransduction. Hybrid hydrogels consisting of alginate and decellularized, demineralised bone extracellular matrix (ALG/ECM) were seeded with Stro-1+ human bone marrow stromal cells (HBMSCs). Dual combinations of growth factors within staged-release polylactic-co-glycolic acid (PLGA) microparticles were added to hydrogels to mimic, in part, the signalling events in bone regeneration: VEGF, TGF-β<sub>3,</sub> PTHrP (fast release), or BMP-2, vitamin D<sub>3</sub> (slow release). Mechanotransduction was initiated using magnetic fields to remotely actuate superparamagnetic nanoparticles (MNP) targeted to TREK1 ion channels. Hybrid hydrogels were implanted subcutaneously within mice for 28 days, and evaluated for bone formation using micro-CT and histology. Control hydrogels lacking HBMSCs, growth factors, or MNP became mineralised, and neither growth factors, HBMSCs, nor mechanotransduction increased bone formation. However, structural differences in the newly-formed bone were influenced by growth factors. Slow release of BMP-2 induced thick bone trabeculae and PTHrP or VitD<sub>3</sub> increased bone formation. However, fast-release of TGF-β<sub>3</sub> and VEGF resulted in thin trabeculae. Mechanotransduction reversed the trabecular thinning and increased collagen deposition with PTHrP and VitD<sub>3</sub>. Our findings demonstrate the potential of hybrid ALG/ECM hydrogel–cell–growth factor constructs to repair bone in combination with mechanotransduction for fine-tuning bone structure. This approach may form a minimally invasive reparative strategy for bone tissue engineering applications.</p></div>","PeriodicalId":100900,"journal":{"name":"Mechanobiology in Medicine","volume":"2 4","pages":"Article 100096"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949907024000597/pdfft?md5=c4df681df7c8d540057e5c6a0cc4449b&pid=1-s2.0-S2949907024000597-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142150304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}